tbuckley/cabot-search huggingface dataset:
Characterizing medical mistrust (MM) in a socio-demographically diverse sample of patients with cancer.
Authors: Cindy Park, Sarah B Bass, Karen J Ruth, Yana Chertock, Katie J Singley, Caseem C Luck, Malak Abuhillo, Aleeha Khan, Shreya Gowda, Erin M Holland, Elizabeth Knight, Shreya Verma, Alexandru-Mircea Rotaru, Abeeda Hussain-Kasim, Agostina Waisfeld, Michael J. Hall
Journal: Journal of Clinical Oncology (2023)

10551 Background: Genetic and genomic testing are increasingly recognized as essential to high quality cancer care. Despite expanded eligibility for testing in recent years, barriers to genomic medicine persist. Notably, growing political and social mistrust risks negatively impacting views of medical institutions, medical professionals and complex technologies, and could undermine acceptance of genetic/genomic testing to guide treatment and identify risk in families. Prior studies have documented disparities and increased MM of genetic counseling and testing among underserved minorities which have been associated with delays or avoidance to care. We sought to identify individual characteristics associated with MM among cancer patients. Methods: A cross-sectional survey of cancer pts from the Fox Chase Cancer Center (FCCC) Burholme Campus (n=105, mixed urban/suburban, primarily insured) and Broad street campus (n=95, primarily urban underserved population) was conducted from 6/22-12/22, using a maximum variation (purposeful) sampling approach. Surveys queried MM using the LaVeist MM Index (MMI, range 0-10, measures healthcare/institution MM) and the Thompson Group Based MM Scale (GBMMS, range 1-5, measures race/ethnic specific MM; suspicion, discrimination, and lack of support subscales). Demographic and disease factors, as well as psychosocial measures (general/genetic health literacy, social support, self-advocacy, conspiratorial thinking, relationship with doctor, and trust in information sources) were also assessed. Medical decision making preference and health literacy were assessed with single validated items. The study was approved by the FCCC IRB #22-8003. Results: Participants had a median age of 62 yrs (range 25-91); 62% were female, 47% African American (AA), 15% Hispanic, 42% married, 47% high school graduate or less, 52% had household income &lt;$50K/yr. Breast (28%), colorectal (16%), and GYN/GU (12%) cancers were the most commonly reported, and 23% reported &gt;1 previous cancer diagnosis. Mean GBMMS was 2.11 (SD 0.80) and mean MMI was 4.63 (SD 1.54). See the table for significant associations. Conclusions: High levels of healthcare institution and race-based MM are associated with socio-demographic vulnerabilities, putting the most vulnerable cancer patients at high risk of making poor health decisions. [Table: see text]
Induction chemotherapy with nedaplatin, docetaxel and 5-fluorouracil followed by concurrent nedaplatin and radiotherapy in locoregionally advanced nasopharyngeal carcinoma: A single arm, open label, phase II clinical trial.
Authors: Chen Fangzheng, Ying Deng, Fang Yang, Meng-Yao Wang, wen-Jing Yin, Jin-Quan Liu, Dong-Ping Chen, Bin Qi
Journal: Journal of Clinical Oncology (2023)

6067 Background: To evaluate the efficacy of induction chemotherapy with nedaplatin, docetaxel and 5-fluorouracil followed by concurrent nedaplatin combined with radical radiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This is a prospective, single-arm, open-label, phase II trial. Patients with aged 18-65 years, newly diagnosed stage III-IVa (except T3-4N0) nasopharyngeal carcinoma were enrolled. Eligible patients received induction chemotherapy with docetaxel (60 mg/m² intravenously on days (D) 1, 22 and 43), Nedaplatin (60 mg/m² intravenously on D 1, 22 and 43) and fluorouracil (600 mg/m² per day as a continuous 120 hours (h) infusion on D 1-5, 22-26 and 43-47) every three weeks for three cycles, thereafter received intensity-modulated radiotherapy (IMRT) concurrently with nedaplatin (100mg/m 2 intravenously on D 1, 22 and (or) 43) every three weeks for two or three cycles. The primary end point was objective response rate (ORR). The secondary end points included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS). Results: Between March 2020 and June 2021, a total of 32 patients with LA-NPC were enrolled. With a median follow-up duration of 14.0 months (IQR 11.7-16.3), 32 patients (100%) achieved ORR at three months after treatment. The 12-month PFS was 95.7% (95% CI 87.3% to 100%) and the 12-month OS was 100%. The most common grade 3 or 4 adverse events during induction chemotherapy were neutropenia (3 [9.4%]), diarrhea (3 [9.4%]) and hepatoxicity (3 [9.4%]), followed by leucopenia (2 [6.3%]) and fatigue (1 [3.1%]). The most common grade 3 or 4 adverse events during concurrent chemotherapy were mucositis (3 [9.4%]), leucopenia (1 [3.1%]), neutropenia (1 [3.1%]) and thrombocytopenia (1 [3.1%]). All of these adverse events were manageable. Conclusions: Induction chemotherapy with nedaplatin, docetaxel and 5-fluorouracil followed by concurrent nedaplatin combined with radical radiotherapy showed promising antitumor activity and manageable toxicities in patients with LA-NPC. Further phase III randomized controlled trials are warranted to validate our findings. Clinical trial information: NCT04834206 .
Alliance A092104: A randomized phase 2/3 study of olaparib plus temozolomide versus investigator’s choice for the treatment of patients with advanced uterine leiomyosarcoma after progression on prior chemotherapy.
Authors: Kristine Peregrino Lacuna, Sumithra J. Mandrekar, Jacob B. Allred, Stephanie A. Berg, Martee Leigh Hensley, Brian Andrew Van Tine, Suzanne George, Gary K. Schwartz, Matthew Ingham
Journal: Journal of Clinical Oncology (2023)

TPS11584 Background: Uterine leiomyosarcoma (uLMS) is an aggressive sarcoma subtype with frequent metastatic relapse. Advanced uLMS is treated with gemcitabine/docetaxel or anthracycline-based regimens. After failure of initial chemotherapy, remaining options provide limited benefit (trabectedin: objective response rate (ORR) 11%, median progression-free survival (mPFS) 4.0 months (mo); pazopanib: ORR 11%, mPFS 3.0 mo; dacarbazine: ORR 9%, mPFS 1.5 mo). 18-23% of uLMS harbor deleterious alterations in homologous recombination (HR) DNA repair genes. HR-deficient cancers are unable to effectively repair double-stranded DNA breaks and may be sensitive to poly ADP-ribose polymerase (PARP) inhibitor-based strategies. In preclinical studies, the combination of temozolomide (T), an alkylating agent, and olaparib (O), a PARP inhibitor, markedly suppressed proliferation of uLMS models. Among 22 uLMS patients with median 3 prior lines, O+T demonstrated mPFS 6.9 mo and ORR 27% (Ingham M. et al. ASCO 2021: #11506). In correlative analysis, alterations in HR genes including PALB2 and RAD51B or absence of RAD51 foci formation by a functional assay were observed in patients with prolonged PFS (Bose S. et al. ASCO 2022: #11509). Based on these results, we designed a randomized phase 2/3 study to further evaluate O+T in advanced, pretreated uLMS. Methods: Alliance for Clinical Trials in Oncology A092104 is a randomized, open-label phase 2/3 clinical trial of O+T versus investigator’s choice in advanced uLMS. Eligible patients have ECOG performance status ≤2, progression on ≥ 2 prior treatment lines and measurable disease. Patients are randomized 1:1 to receive T 75 mg/m2 orally daily + O 200 mg orally twice daily on days 1-7 in 21-day cycles (Arm 1) or investigator’s choice of trabectedin 1.5 mg/m2 over 24 hours every 21 days or pazopanib 400-600 mg orally daily (Arm 2). For phase 2, the primary endpoint is PFS. The design evaluates for an improvement in PFS from 4 mo to 8 mo, requires 70 patients, and yields 90% power and 1-sided alpha 0.10. If phase 2 is positive, phase 3 will enroll. For phase 3, the primary endpoint is overall survival (OS). The design evaluates for an improvement in OS from 13 mo to 23 mo, requires 165 patients (including 70 from phase 2) and yields 90% power with 1-sided alpha 0.025. Secondary endpoints include ORR, duration of response, safety and patient-reported outcomes. Archival tissue will be collected and evaluated with a RAD51 foci formation assay. Genomic sequencing results will be obtained where available. The study opened to accrual in 1/2023. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT05633381 .
A multi-level system quality improvement project to reduce disparities in lung cancer screening: The Sylvester Lung Screening Project.
Authors: Nicole Ann Gay, Melanhy T Da Silva, Vanessa Patricia Vega, Amber Thomassen, Jessica MacIntyre, Georgette Valls-Delgado, Coral Olazagasti, Estelamari Rodriguez
Journal: Journal of Clinical Oncology (2023)

6518 Background: Racial disparities in lung cancer mortality and screening have been well documented in the USA. Annual screening with low dose Computed Tomography (CT) scans is completed in fewer than 6% of the eligible population. Research suggests that many factors contribute to low screening uptake, including barriers to care at patient, clinician, healthcare system, and community levels. In collaboration with the American Cancer Society, the University of Miami/ Sylvester Cancer Center underwent a multi-level system quality improvement (QI) project with the goal to decrease lung cancer screening disparities and improve guideline concordant lung cancer screening across the health care system. Methods: During the one-year multi-level QI project, interventions were put into place to increase lung cancer screening exams via improvements in EMR- identification of eligible patients, patient navigation and expanded provider education services in primary care clinics. Patient level interventions included a marketing campaign, patient navigation, and interpreters to address language barriers. The Patient-interface of the EMR ‘Health Maintenance Gap’ was optimized to alert eligible patients about screening. In addition, a full-time lung cancer screening navigator provided culturally competent, patient-centered counseling, while allowing for an increased capability to manage a higher volume of patients. Provider level interventions included teaching sessions about lung cancer screening and motivational communication skills, and BPA alerts. The primary outcome was the change in the number of screened patients. Results: With the implementation of these multi-level interventions, there was a twenty five percent improvement in the number of lung cancer screening exams completed during the project period January 2022- December 2022 compared to 2021 baseline, from 20 to 25%. The screening rate was highest among Hispanics (12%), followed by Blacks (8%), and Non- Hispanic Whites (NHW) (6%). The majority of LDCT results were Lung RADS Category 1 or 2 (93%). Conclusions: Multi-level interventions that target patients, clinicians, and the health care system can improve lung cancer screening rates in a short-term period. Developing patient-centered, culturally competent interventions is key to reducing disparities in lung cancer screening. This QI intervention was strengthened by tailoring intervention components to the educational primary care physicians and simplifying the referral process. [Table: see text]
Neoadjuvant immunotherapy in sarcomatoid mesothelioma (Alliance A082101).
Authors: Aaron Scott Mansfield, Xiaofei F. Wang, Dennis A. Wigle, Colleen Watt, Gregory A. Masters, Kathryn Kelley, David E. Kozono, Tom Stinchcombe
Journal: Journal of Clinical Oncology (2023)

TPS8602 Background: Sarcomatoid mesothelioma is the most aggressive form of pleural mesothelioma and is associated with the worst prognosis of the histologic variants of this disease. In the Checkmate 743 clinical trial the patients with sarcomatoid mesothelioma who received ipilimumab and nivolumab had survival outcomes that were similar to those of patients with epithelioid mesothelioma. In comparison, the patients with sarcomatoid mesothelioma who received chemotherapy had the worst outcomes in this trial, highlighting the known limited efficacy of chemotherapy against this histologic variant. Checkmate 743 demonstrated that ipilimumab and nivolumab is a new standard of care for non-epithelioid mesothelioma. Surgery typically has not been offered to this group of patients given their historically poor outcomes. With the significant survival gains seen patients with sarcomatoid mesothelioma treated with immunotherapy, we hypothesized that surgery may extend the benefits seen with immunotherapy. Methods: Alliance for Clinical Trials in Oncology A082101 is a prospective, phase 2 nonrandomized clinical trial for patients with sarcomatoid mesothelioma. The co-primary objectives are to determine the percentage of patients with potentially resectable sarcomatoid mesothelioma able to proceed with surgery after neoadjuvant ipilimumab and nivolumab, and the progression-free survival (PFS) at 12 months (12-month PFS). For sample size determination, we assumed that if the true rate of surgery is 75% or greater, it would indicate that neoadjuvant immunotherapy is feasible to be given prior to surgery. On the other hand, if the true rate of surgery is 50% or less it would indicate that neoadjuvant immunotherapy is not worthy of further investigation. Twenty-six (26) eligible patients will be needed to receive neoadjuvant immunotherapy. If 16 or fewer of the 26 eligible patients proceed to surgery, it will be concluded that the experimental therapy is not worthy of further investigation. Otherwise, it will be concluded that the experimental therapy is worthy of further investigation. Safety monitoring will be done through a 6-week run-in for the first 10 patients to assess for pre-operative and post-operative toxicities and complications. Sequential boundaries will be used to monitor severe toxicity and complication rates. Accrual will be halted if excessive numbers of severe toxicity and complications in pre-operative and post-operative phases are seen. Tumor and blood-based biomarkers will be included as exploratory biomarkers. Clinical trial information: NCT05647265 .
Breaking down the divide: An analysis of male breast cancer demographics and survival by race.
Authors: Lekha Yadukumar, Maya Gogtay, Amninder Singh, Namita Sharma
Journal: Journal of Clinical Oncology (2023)

e18593 Background: Male breast cancer (MBC) is rare and comprises &lt; 1% of breast cancers. The incidence of MBC has increased by 40% from 1975 to 2015. It is projected that 2800 new cases of invasive MBCs will be discovered in the US in 2023, and 530 men will die from it. We examined the demographics of MBC and assessed the racial differences influencing survival. Methods: We performed a retrospective cohort study of the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary MBC between 2000 and 2019. Patient demographics, tumor characteristics, and treatments were analyzed by descriptive statistics. Cox proportional hazards regression analysis was performed to identify the factors influencing survival, followed by subgroup analysis by Caucasian (WH) and African American (AA) race. Results: A total of 8373 patients had MBC. AA had 1111 (13.26%) and WH had 6817 (81.41%) MBC cases. AA had a median age of diagnoses of 69 vs WH of 63 years. AA (22.4%) men with MBC had a higher mortality rate (HR 1.44) than WH (16.8%). Older patients were found to be at increased risk of mortality in AA (HR 1.07) and WH (HR 1.17). Tumor size &lt; 20 mm halved the risk of death in WH (HR 0.56), it did not have any significance in AA. Regional lymph node involvement increased the risk of death in AA and WH (HR 4.79 vs 4.05). Poorly differentiated tumors had worse outcomes in WH than AA (HR 2.11 vs. 1.8). ER/PR + status was protective for both races. Mortality was higher in AA men residing in rural areas (HR 1.47) and lower for AA men in urban cities. Marriage improved outcomes for both AA (HR 0.63) and WH (HR 0.61). Surgery alone had better outcomes, AA (HR 0.21) and WH (HR 0.14) than chemotherapy or radiation. Median income was of no significance on survival in either race. Conclusions: Overall, there is a significant difference in incidence and factors influencing survival for male breast cancer between Caucasians and African Americans. Despite the markedly lower incidence of MBC in the AA population, they have poorer outcomes overall. Further studies are required to determine the specific reasons for disparity in their survival. [Table: see text]
Association between real-world, upfront, next-generation sequencing and overall survival (OS) in advanced non–small-cell lung cancer (aNSCLC) in the United States.
Authors: Benjamin Philip Levy, Danny Nguyen, Yu-Hsuan Shih, Magdaliz Gorritz, Beilei Cai, Nydia Caro, Marie Yasuda, Yifan Gu, Chi-Chang Chen, Vincent Pretre, Teddy Rassem Saliba
Journal: Journal of Clinical Oncology (2023)

9117 Background: Multiple biomarker testing strategies exist as the treatments of aNSCLC rapidly evolve. While upfront NGS is considered optimal, this practice has not been universally adopted. Surprisingly, the impact of NGS vs non-NGS approaches on OS is unclear, with the largest study to date demonstrating lack of benefit. We aim to identify the genomic testing strategy associated with the most optimal OS in aNSCLC using data from a large, contemporary electronic health record (EHR) database. Methods: This retrospective study used Flatiron EHR data. Patients diagnosed with aNSCLC between 11 Apr 2019 and 31 Dec 2021 who received systemic therapy were identified and followed from the date of diagnosis to 31 May 2022 or death. Testing methods reported within the patient’s chart were extracted. Methods assessed included NGS (defined as any test type with ‘NGS’ as test name) and non-NGS (defined as PCR, FISH, IHC, and other sequencing methods not containing ‘NGS’). Upfront testing was defined as tests received on or prior to the date of initiation of first-line (1L) therapy. Kaplan-Meier analyses were used to estimate and compare real-world overall survival (rwOS) by testing strategies. Among those with actionable genetic mutations, we also explored rwOS by timing of targeted therapy (TT) initiation. Results: Of a total 13,139 patients, mean age was 69, 49% female, 64% white, 33% Medicare insured, and 88% treated in community setting only. Median follow up time was 9 months. The percentage of patients with upfront NGS increased from 29% in 2019 to 66% in 2022. Median OS (mOS) was longest in patients with upfront NGS compared to those with upfront non-NGS genomic tests (p &lt; 0.05), those with NGS after 1L (p &lt; 0.05), and those with no NGS test ever (p &lt; 0.05) (see table). 19% of patients with upfront NGS vs. 15% of those with upfront non-NGS received TT in 1L; 23% of patients with NGS vs. 19% of those with upfront non-NGS received TT at any line of therapy. In patients with actionable genetic mutations, mOS decreased with later initiation of TT; mOS was not reached (NR) (34.6 – NR) in patients who initiated TT in 1L, 34.7 (29.1 – NR) months in those with 2L TT, and 24.3 (20.3 – 30.1) months in those who initiated TT in 3L. Conclusions: This is the first and largest study to demonstrate that upfront NGS testing leads to better OS when compared to upfront non-NGS genomic testing, later NGS, or no-NGS in aNSCLC. In line with these results, we also found an OS benefit associated with earlier TT initiation. These results highlight the significant impact of upfront NGS testing and underscore for the need for both education and wider accessibility of NGS testing. [Table: see text]
Transplant teeter-totter: How hematologists communicate the high risk, high reward nature of allogeneic hematopoietic cell transplant with patients.
Authors: Rachel Rodenbach, Thorunn Halldora Thordardottir, Toby Christopher Campbell
Journal: Journal of Clinical Oncology (2023)

e24189 Background: While allogeneic hematopoietic cell transplant (HCT) offers a chance of cure for many patients with aggressive blood cancers, it carries many risks. Little is known about how hematologists communicate this uncertainty with patients. In this secondary analysis from a telemedicine study assessing how transplant hematologists facilitate shared decision making with patients, we evaluated how physicians discuss the high risk, high reward concept of allogeneic HCT. Methods: This is a qualitative analysis of transcribed video-recorded virtual encounters of transplant hematologists with patient actors. We recruited US hematologists who routinely perform allogeneic HCT via email. Participants conducted up to an hour-long video encounter with an actor trained to portray a 67-year-old man recently diagnosed with high-risk myelodysplastic syndrome and referred for specialty hematology consultation for discussion of treatment options. Results: Transcripts from 33 hematologists (mean age 46 +/- 11 years; 61% male) were available at the time of analysis. Hematologists frequently used “teeter-totter” language that oscillated between optimistic encouragement and cautious hesitancy about allogeneic HCT: HCT represented the best and only chance for cure, but it was dangerous, required sacrifice, and did not ensure long term survival. Many hematologists used tentative hedging to describe HCT’s intent for possible (rather than certain) cure, and many detailed the effect of potential undesirable complications on survival and quality of life. They also acknowledged that given HCT’s unpredictability and complexity, prognostication for any individual patient was difficult if not impossible, especially early on. The teeter-totter language frequently occurred within the same sentence or speaker turn (e.g. it may “give[] you a cure, but it comes at a price”) and also played out more gradually throughout the encounter both in exchanges between hematologist and patient and by the hematologist. With respect to decision making, some hematologists expressed their goal for the patient to understand the teeter-totter of transplant in order to make a well-informed decision based upon the patient’s personal risk tolerance/aversion. Others proposed that they share an acceptance of the teeter-totter and together deal with complications one step at a time along the transplant journey. Many reinforced that transplant offered the best chance for long term survival despite the risks and that they would do everything they could to help the patient achieve this. Conclusions: Hematologists use “teeter-totter” language to express uncertainty, hope, and caution about the high risk, high reward nature of allogeneic HCT. This language is used to prepare patients for unpredictable and uncontrollable aspects of the transplant journey and to inform decision making.